ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Myofibroblasts in murine cutaneous fibrosis originate from adiponectin-positive intradermal progenitors.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 323 citations in OpenAlex.
- Epoprostenol up-regulates serum adiponectin level in patients with systemic sclerosis: therapeutic implications.Archives of dermatological research · 2021Trial
- Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.The Journal of investigative dermatology · 2017Trial
- Layer-Specific Dermal and Subcutaneous Delivery via Modular LNP-Hydrogel-Integrated Threaded Microneedles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DPP4 Substrate Supplementation Protects From WNT-Induced Lipid Depletion in Dermal Adipocytes.Experimental dermatology · 2026Article
- Lipodystrophy and adipose tissue recovery are mediated by the Wnt/lipogenesis axis during skin fibrosis.The Journal of pathology · 2026Article
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- PDGF signaling regulates the adipocyte-to-fibroblast transition in wound healing.Cell reports · 2026Article
- Wnt/β-catenin signaling regulates fibrotic atrophy of intra-articular adipose tissue in post-traumatic osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Adipocyte-specific deletion of sine oculis homeobox homolog 1 inhibits lipolysis and reduces skin fibrosis.JCI insight · 2026Article
- A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model.JCI insight · 2026Article
- Adipocytes as core drivers of skin aging and novel targets for regeneration.Biogerontology · 2026Review
- Expression and clinical significance of fatty acid metabolism-related genes in PBMCs of SSc patients.Clinical rheumatology · 2026Article
- Dedifferentiation of Mature Adipocytes and Their Future Potential for Regenerative Medicine Applications.Biomedicines · 2026Review
- Cellular gatekeepers of infected wounds: the dual role of adipocytes in coordinating immunity and regeneration.Frontiers in immunology · 2026Review
- Concentrated Micronized Fat Ameliorates Skin Fibrosis in Bleomycin-Induced Murine Model and Enhances Fat Graft Survival.Aesthetic plastic surgery · 2025Article
- Article
- Mirabegron treatment reduces myofibroblasts and CXCR2 expression in adipose tissue in obesity.Molecular medicine (Cambridge, Mass.) · 2025Article
- Revolutionizing Autoimmune Research: The Role of Caveolin-1.Immunity, inflammation and disease · 2025Review
- Atgl-Dependent Adipocyte Lipolysis Promotes Lipodystrophy and Restrains Fibrogenic Responses during Skin Fibrosis.The Journal of investigative dermatology · 2025Article
- Wnt Activation in Mature Dermal Adipocytes Leads to Lipodystrophy and Skin Fibrosis via ATGL-Dependent Lipolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
129 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveAccumulation of myofibroblasts in fibrotic skin is a hallmark of systemic sclerosis (SSc; scleroderma), but the origins of these cells remain unknown. Because loss of intradermal adipose tissue is a consistent feature of cutaneous fibrosis, we sought to examine the hypothesis that myofibroblasts populating fibrotic dermis derive from adipocytic progenitors.
methodsWe performed genetic fate mapping studies to investigate the loss of intradermal adipose tissue and its potential role in fibrosis in mice with bleomycin-induced scleroderma. Modulation of adipocytic phenotypes ex vivo was investigated in adipose tissue-derived cells in culture.
resultsA striking loss of intradermal adipose tissue and its replacement with fibrous tissue were consistently observed in mice with bleomycin-induced fibrosis. Loss of adipose tissue and a decline in the expression of canonical adipogenic markers in lesional skin preceded the onset of dermal fibrosis and expression of fibrogenic markers. Ex vivo, subcutaneous adipocytes were driven by transforming growth factor β to preferentially undergo fibrogenic differentiation. Cell fate mapping studies in mice with the adiponectin promoter-driven Cre recombinase transgenic construct indicated that adiponectin-positive progenitors that are normally confined to the intradermal adipose tissue compartment were distributed throughout the lesional dermis over time, lost their adipocytic markers, and expressed myofibroblast markers in bleomycin-treated mice.
conclusionThese observations establish a novel link between intradermal adipose tissue loss and dermal fibrosis and demonstrate that adiponectin-positive intradermal progenitors give rise to dermal myofibroblasts. Adipose tissue loss and adipocyte-myofibroblast transition might be primary events in the pathogenesis of cutaneous fibrosis that represent novel potential targets for therapeutic intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.